Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease that causes chronic, progressive, and irreversible fibrosis in the lungs. It is characterized by alveolar damage and exaggerated fibrous tissue production that results in obliteration of lung parenchyma and subsequent lung dysfunction (see Wilson, M. S. and T. A. Wynn (2009). “Pulmonary fibrosis: pathogenesis, etiology and regulation.” Mucosal Immunol 2(2): 103-121). Currently, around 5 million people worldwide are affected by IPF with over 128,000 patients in the United States with a median survival time of approximately 2.5 years from the time of diagnosis (see Raghu, G., D. Weycker, J. Edelsberg, W. Z. Bradford and G. Oster (2006). “Incidence and prevalence of idiopathic pulmonary fibrosis.” Am J Respir Crit Care Med 174(7): 810-816). Although two anti-fibrotic drugs, pirfenidone and nintedanib, have been approved for the treatment of IPF, treatment options are still limited for this severe disease (see Harari, S. and A. Caminati (2015). “Idiopathic pulmonary fibrosis: from clinical trials to real-life experiences.” Eur Respir Rev 24(137): 420-427).
Hypoxemia and hypoxia arise in patients with IPF because the body (or a tissue, or a cell) is deprived of oxygen One of the clinical manifestations of hypoxia is exertional breathlessness for which there are no available drugs to date (see Baddini Martinez, J. A., T. Y. Martinez, F. P. Lovetro Galhardo and C. A. de Castro Pereira (2002). “Dyspnea scales as a measure of health-related quality of life in patients with idiopathic pulmonary fibrosis.” Med Sci Monit 8(6): CR405-410; see also Parshall, M. B., R. M. Schwartzstein, L. Adams, R. B. Banzett, H. L. Manning, J. Bourbeau, P. M. Calverley, A. G. Gift, A. Harver, S. C. Lareau, D. A. Mahler, P. M. Meek, D. E. O'Donnell and D. American Thoracic Society Committee on (2012). “An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea.” Am J Respir Crit Care Med 185(4): 435-452).
Oxygen deprivation resulting from hypoxemia and/or hypoxia can, in turn, cause severe organ damage and even death. Therefore, there continues to be a significant need for drugs useful in the treatment of above diseases or conditions.